The human mesothelioma cell lines established by this laboratory represent a sizeable number of examples of this relatively rare tumor type. Accordingly, these cell lines have been analyzed for the status of the retinoblastoma gene, the K- and H-ras genes and the p53 gene. The findings indicate that, while involvement of the retinoblastoma gene in this disease is unlikely, mutations in the p53 gene may occur. Utilizing the immortalized, nontumorigenic human mesothelial cell line, MET-5A, developed at LHC, we have tested the tumorigenic potential of EJ-ras and the human platelet-derived growth factor (PDGF)-A and -B chain genes. The results to date indicate that overexpression of both mutated ras and the PDGF-A chain can convert this cell line to tumorigenicity. It is of interest that the tumors induced by these different genes differ both with respect to their growth rate in vivo and their histopathological type, resembling either the epithelial or spindeloid type of human mesothelioma.